The development of food search behavior by rats: the effects of hippocampal damage and haloperidol

Abstract

Introduction:
The aim of the study was to see if some of the effects of hippocampal brain damage on attention-related function may be mediated perhaps trans-synaptically in the dopamine (DA) system.
Methods:
A food search task in a 16-hole board was developed (based on search studies used to investigate the avian hippocampus (Oades 1976), but suitable for rodents). Food-deprived rats were required to locate 4 pellets located in 4 of 16 holes in an enclosed arena.
Three groups of animals were studied in 11 test sessions : - rats with bilateral hippocampal aspiration lesions, bilateral neocortical damage (overlying the hippocampus), and an unoperated group. Half of each group received haloperidol (DA D2 antagonist) and half saline before sessions 4 through 10. No injections were administered on the first three or the last test session.
Results:
1/ Animals with hippocampal damage visited more non-food holes (errors) than the controls, AND did not develop consistent sequences of food-hole visits as the other animals did.
2/ In unoperated controls haloperidol reduced the number of preferred sequences of food-hole visits, WITHOUT affecting the efficiency of performance as measured by the number of non-food-holes visited (i.e., the number of errors did not increase).
3/ Haloperidol treatment of those with hippocampal damage
reduced the number of non-food-hole visits (i.e. reduced the number of errors made in comparison to the saline treated animals with hippocampal damage).
Conclusions:
It is likely that hippocampal damage incurs increased DA activity elsewhere that for the search task is not adaptive and brings about an increase in the number of errors made. This contrasts with the normal development of a consistent sequence of food-hole visits (individually specific) - one form of working memory aid - that is disrupted by haloperidol and by hippocampal damage. Neuroleptic treatment of the hippocampal animals did not reinstate this preferred sequence but by dampening DA activity (reducing switching between alternatives, Oades 1985) improved attention-related search performance by decreasing the number of erros made.
This result may be seen post-hoc as a model for some of the functions disturbed in schizophrenia - where there is evidence for impaired medial temporal lobe function (hippoicampus, parahippocampal gyrus) and often hyper-active DA systems, sometimes ameliorated through neuroleptic treatment (see further studies by Lipska and Weinberger: e.g. Lipska et al. 1992; 1993, 1994, 1995; Sams-Dodd et al., 1997; Wood et al., 1997).